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Cell Metabolism Publishes Novel TGR5-Mediated Mechanism for the Treatment of Diabetes and Obesity
Date:9/1/2009

a DPP4 inhibitor such as sitagliptin.
  • INT-777 normalizes glucose tolerance in obese, insulin resistant (DIO) and diabetic (db/db) mice; the treated mice maintain normal insulin levels and glucose uptake in liver and muscle.
  • INT-777 prevents weight gain and fat accumulation in mice on a high fat diet by increasing energy expenditure and fat burning; liver function is also protected with reduced steatosis, fibrosis and serum markers of liver damage in the treated mice.
  • Professor Pellicciari, a co-author on the paper, commented, "Years of concerted discovery efforts and proprietary know-how in bile acid chemistry have resulted in our ability to rationally design molecules that are highly selective for bile acid receptors. The realization of this in the novel TGR5 agonist INT-777 and the characterization of its mechanism of action represent an important milestone in the establishment of a novel class of therapeutic agents targeting this receptor."

    Professor Johan Auwerx, who has led the field in uncovering the role of the TGR5 receptor and representing the lead authors at EPFL, added, "Our collaboration with the joint Intercept-Pellicciari team has been extremely fruitful. We are very pleased with the performance of INT-777, a compound that has allowed us to further elucidate this critical mechanism of TGR5 regulated GLP-1 release in the gut."

    Dr. Mark Pruzanski, founder, President and CEO of Intercept and a co-author on the paper, commented further, "Diabetes, obesity and other associated metabolic disorders are reaching epidemic proportions. At Intercept we are uniquely positioned to exploit the therapeutic potential of modified bile acids, molecules that nature has designed to play a central role in the maintenance of metabolic homeostasis. In this context, TGR5 has emerged as an important target and INT-777 as an excellent candidate that we plan to advance into t
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    SOURCE Intercept Pharmaceuticals, Inc.
    Copyright©2009 PR Newswire.
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